Generic Everolimus Receives FDA Approval for Treatment of Tuberous Sclerosis Complex

Generic everolimus tablets for oral suspension (TFOS), 2 mg, 3 mg, and 5 mg (Afinitor Disperz; Breckenridge Pharmaceutical Inc.) were granted final approval by the FDA for adult and pediatric patients aged 1 year and older with tuberous sclerosis complex (TSC) for the treatment of subependymal giant cell astrocytoma (SEGA) that cannot be curatively resected and that requires therapeutic intervention.

Tuberous sclerosis complex written on easel | Image Credit: © Yurii Kibalnik - stock.adobe.com

TSC is a rare, non-cancerous genetic disorder that is characterized by the growth of benign tumors in the brain and other parts of the body, such as the spinal cord, nerves, eyes, lung, heart, kidneys, and skin. It is a lifelong condition with no cure; however, there are therapies available to address symptoms, which include tumors, seizures, cognitive difficulties, behavioral difficulties, and autism spectrum disorder, as well as various kidney conditions.¹

Everolimus is an oral kinase inhibitor that was approved by the FDA in 2018 for the adjunctive treatment of adult and pediatric patients aged 2 years and over with TSC-associated partial-onset seizures. In January 2025, it received additional approval for adult and pediatric patients ages 1 and older based on data from the randomized, double-blind, placebo-controlled phase 3 study, EXIST-1 (NCT00789828).^2-6

In the trial, 117 patients were randomly assigned in a 2:1 ratio to receive either 4.5 mg/m² per day (titrated to achieve blood trough concentrations of 5–15 ng/mL) of everolimus (n = 78) or placebo (n = 39). Treatment with everolimus resulted in 35% of patients achieving a 50% reduction in the volume of SEGA versus none in the placebo group (difference 35%, 95% CI 15–52; one-sided exact Cochran-Mantel-Haenszel test, P<.0001).^4,7

The safety profile was favorable, with grade 1 and 2 adverse events being the most common. These included mouth ulceration (32%), stomatitis (31%), convulsion (23%), and pyrexia (22%).^4,7

The FDA’s approval of generic everolimus tablets for oral suspension offers a new, cost-effective option for patients with TSC-associated SEGA, expanding access to an essential treatment. As research continues to refine targeted therapies for rare diseases like TSC, this approval underscores the importance of advancing treatment options that improve patient outcomes while maintaining a manageable safety profile.

REFERENCES

1. Tuberous sclerosis complex. National Institute of Neurological Disorders and Stroke. July 19, 2024. Accessed January 29, 2025. https://www.ninds.nih.gov/health-information/disorders/tuberous-sclerosis-complex#:~:text=What%20is%20tuberous%20sclerosis%20complex,heart%2C%20kidneys%2C%20and%20skin

2. Breckenridge announces final FDA approval for Everolimus tablets for oral suspension, AB-rated to AFINITOR DISPERZ®. PR Newswire. January 29, 2025. Accessed January 29, 2025. https://www.prnewswire.com/news-releases/breckenridge-announces-final-fda-approval-for-everolimus-tablets-for-oral-suspension-ab-rated-to-afinitor-disperz-302363514.html

3. FDA approves everolimus for tuberous sclerosis complex-associated partial-onset seizures. FDA. April 11, 2018. Accessed January 29, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-everolimus-tuberous-sclerosis-complex-associated-partial-onset-seizures

4. FDA grants approval to generic extended-release memantine/donepezil and everolimus. Pharmacy Times. January 23, 2025. Accessed January 29, 2025. https://www.pharmacytimes.com/view/fda-grants-approval-to-generic-extended-release-memantine-donepezil-and-everolimus

5. Amneal Receives U.S. FDA Approval for Memantine/Donepezil Extended-Release Capsules and Everolimus Tablets for Oral Suspension, and Tentative U.S. FDA Approval for Rifaximin. Businesswire. January 23, 2025. Accessed January 29, 2025. https://www.businesswire.com/news/home/20250123740756/en/Amneal-Receives-U.S.-FDA-Approval-for-MemantineDonepezil-Extended-Release-Capsules-and-Everolimus-Tablets-for-Oral-Suspension-and-Tentative-U.S.-FDA-Approval-for-Rifaximin

6. Efficacy and safety of everolimus (RAD001) in patients of all ages with subependymal giant cell astrocytoma associated with tuberous sclerosis complex (TSC)(EXIST-1) (EXIST-1). Updated February 3, 2016. Accessed January 29, 2025. https://clinicaltrials.gov/study/NCT00789828

7. Franz D, Belousova E, Sparagana S, et al. Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial. The Lancet. January 12, 2013. doi: 10.1016/S0140-6736(12)61134-9